孕妇血清邻苯二甲酸单酯水平与甲状腺功能关联研究

发布时间：2018-09-17 11:59

【摘要】：背景邻苯二甲酸酯（PAEs）的大量使用，可通过消化道、呼吸道、皮肤等途径进入体内，导致人体及动物的广泛暴露。孕妇作为易感人群，其体内的暴露不仅会影响自身健康还会导致胎儿的宫内暴露，产生生殖和发育的直接损害，新近的研究还发现PAEs对甲状腺功能的干扰作用，提示孕期PAEs暴露潜在的胎儿神经系统发育损害和出生后智力与行为损伤。然而，在我国目前关于大样本的孕妇PAEs暴露对甲状腺功能的研究缺乏。目的描述安徽省马鞍山市孕妇孕期血清邻苯二甲酸单酯的一般水平及其随孕周发生的变化，分析孕期母体血清邻苯二甲酸单酯水平的影响因素，探讨孕期母体邻苯二甲酸单酯水平与甲状腺功能之间的关联，从而进一步为人群队列研究提供实验和理论基础。方法在中国安徽出生队列（China-Anhui Birth Cohort Study，C-ABCS）的马鞍山市样本人群中选取1492名孕产妇进行研究。该研究的现场调查于2008年10月－2010年12月进行，孕妇报告了社会人口统计学资料；妊娠史和既往疾病史；孕早期职业与生活环境以及生活方式等信息。检验科的专业人员采集孕妇空腹外周静脉血样本。该研究的实验室检测于2011年12月－2013年08月进行，用固相萃取－高效液相串联质谱法（HPLC-MS）测定孕妇血清中的邻苯二甲酸单乙酯（MEP），邻苯二甲酸单丁酯（MBP）和邻苯二甲酸单（2-乙基己基）酯（MEHP）的水平，评估其暴露特点及相应变化。使用2检验和多因素Logistic回归分析安徽省孕妇邻苯二甲酸单酯暴露的影响因素。Pearson相关和多元线性回归模型用于分析邻苯二甲酸单酯与甲状腺功能的关联。结果MEP、MBP和MEHP的检出率分别为86.7%、99.8%和100.0%，其中位数浓度分别为0.16ng/mL，5.97ng/mL和5.94ng/mL。多因素Logistic回归结果显示孕期高MEP水平的影响因素为孕5～8周；高MBP水平的影响因素为孕5～8周，本科以上教育程度，流产史，，妇科感染性疾病史和孕前半年灭蚊剂的使用史；高MEHP水平的影响因素为孕5～8周，孕妇年龄30岁以上，城镇居住地，孕前灭蚊剂的使用史。孕5～8周时，孕妇血清中MEP、MBP和MEHP的中位数分别为0.19、6.55和8.70ng/mL，MEP分别与MBP和MEHP呈正相关（r＝0.20，P0.001；r＝0.28，P＜0.001），MBP与MEHP呈正相关（r＝0.35，P＜0.001）；孕9～12周时，孕妇血清中MEP、MBP和MEHP的中位数分别为0.15、5.75和5.94ng/mL，MEP分别与MBP和MEHP呈正相关（r＝0.12，P＜0.01；r＝0.14，P＜0.001），MBP与MEHP呈正相关（r＝0.26，P＜0.001）；孕≥13周时，孕妇血清中MEP、MBP和MEHP的中位数分别为0.17、5.90和5.11ng/mL，MEP与MBP和MEHP呈正相关（r＝0.15，P＜0.001；r＝0.10，P＜0.05），MEHP与MBP呈正相关（r＝0.33，P＜0.001）。在不同孕周组中，MBP和MEHP均与总甲状腺素（TT4）呈负相关，相关具有显著统计学意义。多元线性回归模型中，控制潜在影响因素后，孕5～8周时，MBP与TT4的回归系数为-0.020（95%CI：-0.043～0.002；P＝0.079），MEHP与TT4的回归系数为-0.030（95%CI：-0.054～-0.005；P＜0.05）；孕周为9～12周时，MBP与TT4的回归系数为-0.032（95%CI：-0.049～-0.014；P＜0.001），MEHP与TT4的回归系数为-0.042（95%CI：-0.062～-0.022；P＜0.001）；孕周≥13周时，MBP与TT4的回归系数为-0.026（95%CI：-0.045～-0.008；P＜0.01），MEHP与TT4的回归系数为-0.044（95%CI：-0.066～-0.021；P＜0.001）。结论孕期妇女已经普遍暴露于邻苯二甲酸单酯，孕周越大的孕妇，邻苯二甲酸单酯水平越低。孕期不同的邻苯二甲酸单酯暴露水平影响因素不同，需要关注不良妊娠史和家庭化学品的使用与PAEs的关系，教育准备妊娠的妇女避免和减少塑料制品的使用。孕妇血清的邻苯二甲酸单酯水平与母体TT4浓度呈负相关。本研究结果为PAEs类物质的管理和其造成的效应提供了基础资料，但其具体的暴露途径与剂量评估及其对甲状腺功能干扰作用机制等，还需要多学科协作研究。
[Abstract]:Background Phthalate esters (PAEs) are widely used and can enter the body through the digestive tract, respiratory tract, skin and other channels, resulting in extensive exposure of human beings and animals. As a susceptible group, pregnant women exposed in vivo not only affect their own health, but also lead to fetal exposure in utero, resulting in direct damage to reproduction and development. Recent studies also It was found that PAEs interfered with thyroid function, suggesting that PAEs exposure during pregnancy may lead to potential fetal nervous system development impairment and postnatal intellectual and behavioral impairment.
Objective To describe the general level of serum monophthalate and its changes with gestational weeks in pregnant women in Maanshan City, Anhui Province, and to analyze the influencing factors of maternal serum monophthalate levels during pregnancy, and to explore the relationship between maternal monophthalate levels and thyroid function during pregnancy, so as to be a cohort study. Research provides experimental and theoretical basis.
Methods A total of 1 492 pregnant and lying-in women in Ma'anshan, Anhui Birth Cohort Study (C-ABCS) were selected for the study. Laboratory tests were carried out from December 2011 to August 2013 to determine monoethyl phthalate (MEP) and monobutyl phthalate (MBP) in maternal serum by solid phase extraction-high performance liquid chromatography-mass spectrometry (HPLC-MS). Pearson correlation and multivariate linear regression models were used to analyze the relationship between monophthalate and thyroid function.
Results The detection rates of MEP, MBP and MEHP were 86.7%, 99.8% and 100.0% respectively, and the median concentrations were 0.16 ng/mL, 5.97 ng/mL and 5.94 ng/mL, respectively. The influencing factors of high MEHP level were 5-8 weeks of gestation, age of pregnant women over 30 years old, residence in cities and towns, and use history of mosquito killers before pregnancy.The median of MEP, MBP and MEHP in serum of pregnant women were 0.19, 6.55 and 8.70 ng/mL at 5-8 weeks of gestation, and MEP was positively correlated with MBP and MEHP respectively (r = 0.20, P 0.001). Medians of serum MEP, MBP and MEHP were 0.15, 5.75 and 5.94 ng/mL at 9-12 weeks gestation, and MEP was positively correlated with MBP and MEHP (r = 0.12, P < 0.01; r = 0.14, P < 0.001), and MBP was positively correlated with MEHP (r = 0.26, P < 0.001) at 13 weeks gestation. Median values of MEP, MBP and MEHP were 0.17, 5.90 and 5.11 ng/mL, respectively. MEP was positively correlated with MBP and MEHP (r = 0.15, P < 0.001; r = 0.10, P < 0.05), and MEHP was positively correlated with MBP (r = 0.33, P < 0.001). MBP and MEHP were negatively correlated with total thyroid hormone (TT4) in different gestational weeks, with significant correlation. In the model, the regression coefficients of MBP and TT4 were - 0.020 (95% CI: - 0.043 - 0.002; P = 0.079) and - 0.030 (95% CI: - 0.054 - 0.005; P < 0.05) at 5 to 8 weeks of gestation and - 0.032 (95% CI: - 0.049 - 0.014; P The regression coefficients of MBP and TT4 were - 0.026 (95% CI: - 0.045 ~ - 0.008; P < 0.01) and - 0.044 (95% CI: - 0.066 ~ - 0.021; P
Conclusion Pregnant women have been generally exposed to monophthalate, the greater the gestational age, the lower the level of monophthalate. Different exposure levels of monophthalate during pregnancy have different influencing factors. It is necessary to pay attention to the relationship between adverse pregnancy history and the use of family chemicals and PAEs. The results of this study provide basic information for the management of PAEs and their effects, but the specific exposure pathway and dose assessment and its mechanism of thyroid function disturbance need to be studied by multi-disciplinary collaboration.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R714.256

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